Analyte concentration determination in biological fluids is of ever increasing importance. Such assays find use in a variety of applications and settings, including clinical laboratory testing, home testing, etc., where the results of such testing play a prominent role in the diagnosis and management of a variety of disease conditions. Common analytes of interest include glucose for diabetes management, cholesterol for monitoring cardiovascular conditions, and creatinine, creatine, urea and the like. In response to this growing importance of analyte concentration detection, a variety of analyte detection protocols and devices for both clinical and home use have been developed.
One type of method that is employed for analyte detection is an electro-chemical-based method. In such methods, a sample of a substance to be tested, e.g., a biological substance typically in aqueous liquid form, e.g., blood, is placed into a reaction zone in an electrochemical cell made up of at least two electrodes, i.e., a counter/reference electrode and a working electrode. Most electrochemical biosensors employ one of three conventional methodologies: coulometry (measuring charge), chronoamperometry (measuring current), and chronopotentiometry (measuring potential or voltage). In coulometry and chronoamperometry, typically, a redox reagent system is present within the reaction zone. Such a reagent system includes one or more enzymes and a mediator. The enzyme usually functions to oxidize the analyte of interest. When the sample is deposited into the electrochemical cell, the targeted analyte comes into contact with the enzyme(s) and reacts therewith forming reduced enzyme. The mediator in turn reacts with and regenerates the oxidized form of the enzyme, itself being reduced. The reduced mediator is then oxidized at the working electrode. The resultant charge or current generated by such a reaction is measured. The magnitude of the measured charge or current is proportional to the concentration of the target analyte present in the biological substance being tested.
The above-described electrochemical cell is commonly used in the form of a disposable test strip on which the biological sample is deposited and which is receivable within a meter by which the analyte concentration is determined. Examples of assay systems that employ these types of test strips, often referred to as biosensors, and meters may be found in U.S. Pat. Nos. 6,129,823, 6,773,671, 6,143,164, 6,592,745, 6,338,790, 6,503,381, 5,628,890, 5,820,551, 6,251,260, 6,551,494, 6,863,800, and U.S. patent application Ser. No. 11/147,532.
For successful commercialization as a consumer product, user convenience is key. The less intrusive the testing activity, the more likely patients will comply with required testing regime and the better their medical conditions are able to be managed. One way of minimizing the intrusiveness of analyte measurements is to provide rapid assays.
However, the presence of hematocrit, i.e., red blood cells, within the blood may affect the accuracy of measuring a targeted analyte, e.g., glucose, using rapid assay biosensors for use with whole blood samples. This is so as hematocrit tends to change the rate of diffusion of species within the blood sample or otherwise hinder the performance of the test. The sensitivity to hematocrit level is generally exaggerated with shorter assay times. Accordingly, the presence of hematocrit represents a significant challenge to the development of short assay systems for the measurement of blood analytes. While there are conventional systems that afford relatively short assays which also perform a secondary assay that estimates hematocrit level for the purpose of signal compensation; such secondary assay adds to the overall assay time, presenting a significant drawback.
Conventional electrochemical detection techniques have other drawbacks as well, particularly with respect to the measurement of blood analytes. Because sensors employing single potential step techniques are not capable of decoupling multiple signals, those configured to determine glucose concentration in blood may be susceptible to influence from other interfering substances that may be present in the sample and oxidized at voltages similar to, or lower than that required for oxidation of the chosen mediator. As such, any of these interfering substances may be mistakenly identified as the analyte of interest—for example glucose in certain systems. These effects will give artificially elevated estimates of the analyte concentration. Additionally, conventional analyte detection systems are typically capable of, or limited to measuring only a single analyte.
Environmental factors such as temperature and humidity, that can influence sample temperature and evaporation, may also have an effect the accuracy of analyte measurements. Most prior art analyte measurement systems rely solely on simple electronic components (such as a thermistor embedded in a meter) to compensate for errors that might arise due to temperature. Relative to the rapid temperature equilibration of a small sample drop, thermistors are relatively slow in sensing changes in temperature. See, for example, U.S. Patent Application Publication No. 2003/0159945. This is particularly important where the meter may be used shortly after being moved from a relatively warm place to a relatively cooler one or visa versa. In this case, an incorrect temperature compensation factor may be applied to the test result. Some manufacturers have gone to some length to address the influences of temperature in analyte measurements by adding additional components, e.g., secondary thermistors, and more complex circuitry in an attempt to prevent such errors. Such electronic hardware increases costs and space requirements of an analyte measurement meter.
Accordingly, it is desirable to develop an easy to use analyte sensor capable of performing a rapid yet accurate assay to determine the concentration of one or more analytes from a single blood sample, independent of the blood hematocrit level and environmental conditions at the time of testing. Such a sensor would be particularly useful and beneficial for blood analyte measurements such as glucose concentration.